NOVOBIOCIN ACTIVATES THE MATING RESPONSE IN YEAST THROUGH THE ALPHA-PHEROMONE RECEPTOR, STE2P

In a previous publication we reported the isolation of several yeast m utants sensitive to the coumarin drug novobiocin. Here we characterise the wild-type gene (NBS5), obtained by rescuing a novobiocin-sensitiv e nbs5 strain to natural novobiocin resistance. We show that nbs5 is a llelic to the previously characterised gene sst2, conferring super-sen sitivity to the mating pheromones. Although nbs5/sst2 cells of both ma ting types are super-sensitive to the opposite mating pheromone, only cells of mating-type a are sensitive to novobiocin. We show that the e ntire effect of the drug is mediated through Ste2p, the ru-pheromone r eceptor. Thus, novobiocin is a functional agonist of Ste2p, and may id entify a potentially useful interaction between coumarin drugs and the family of G-protein-coupled receptors.